Every year more than 18 million patients experience sepsis caused by systemic blood-borne infection, and more than 6 million of these people die. Mortality rates from sepsis in intensive-care units range from 20 to 60% worldwide, and one retrospective study revealed that 20% of patients with septic shock were initially treated with inappropriate antibiotic therapy (Kumar et al., Chest 2009; 25: 733). This is largely because it takes days to obtain a rigorous diagnosis of pathogen type, even in state-of-the art clinical microbiology laboratories. Moreover, patients who initially receive incorrect therapies exhibit a 5-fold lower survival rate than those who are treated with optimal therapy from early in the course of the disease. In fact, in one study it was shown that the risk for in-hospital mortality increased by 9% for every hour of delay before the correct antibiotic regimen was administered (Garnacho-Montero et al., Critical Care 2006; 10:R111). Thus, the speed of pathogen diagnosis in a patient with a blood-borne microbial infection can mean the difference between life and death. The current state-of-the-art for detection of a microbial infection in blood, which has essentially remained unchanged for the past thirty years, is to culture the blood in a hospital or commercial clinical microbiology laboratory. Liquid cultures can permit detection of the existence of some type of growing organism in the fluid within 16 to 30 hours (based on the analysis of more than 50,000 blood cultures carried out in one year at the Brigham and Women's Hospital clinical microbiological laboratory). This assay is not quantitative and without knowledge of the type of pathogen and their specific antibiotic sensitivities, only wide-spectrum antibiotics can be administered at this time, which are suboptimal at best. To identify the specific type of pathogen, and to carry out sensitivity testing to determine their responses to various potential antibiotic therapies, the pathogens growing in liquid medium must then be transferred to other growth media (e.g., agar plates). The total time for full diagnosis and sensitivity testing is commonly 3-7 days and empiric antibiotic treatment based on clinical symptoms is started well before the results of the antibiotic sensitivity are obtained, often within 1-3 hours after blood cultures are first drawn from the patient.
Many patients with septicemia or suspected septicemia exhibit a rapid decline over a 24-48 hour period. Thus, rapid and reliable diagnostic and treatment methods are essential for effective patient care. Unfortunately, current antimicrobial susceptibility testing techniques generally require a prior isolation of the microorganism by culture (e.g., about 12 to about 48 hours), followed by a process that requires another about 6 to about 24 hours. For example, a confirmed diagnosis as to the type of infection, traditionally requires microbiological analysis involving inoculation of blood cultures, incubation for 16-24 hours, plating the causative microorganism on solid media, another incubation period, and final identification 1-2 days later. Even with immediate and aggressive treatment, many patients develop multiple organ dysfunction syndrome and eventually death.
Every hour lost before a correct treatment is administered can make a crucial difference in patient outcome. Consequently, it is important for physicians to determine rapidly if the patient indeed has sepsis, and if so, what antibiotics would be effective for the treatment. For example, an appropriate antimicrobial therapy that can be instated within 6 hours of the onset of sepsis can positively impact patient outcome. However, the current practice, i.e., blood culture, takes two days or more to yield an answer, which quite often proves too long. Accordingly, there is a strong need for a more rapid antibiotic sensitivity testing, preferably one that can identify specific antibiotic susceptibilities within only a few hours after blood samples are first drawn. A rapid test of this type would therefore permit physicians to initiate the optimal drug therapy from the start, rather than starting with a suboptimal or completely ineffective antibiotic, hence greatly increasing clinical responsiveness.